Abstract

Transcranial direct current stimulation (tDCS) is an innovative technique recently shown to improve language outcomes even in neurodegenerative conditions such as primary progressive aphasia (PPA), but the underlying brain mechanisms are not known. The present study tested whether the additional language gains with repetitive tDCS (over sham) in PPA are caused by changes in functional connectivity between the stimulated area (the left inferior frontal gyrus (IFG)) and the rest of the language network. We scanned 24 PPA participants (11 female) before and after language intervention (written naming/spelling) with a resting-state fMRI sequence and compared changes before and after three weeks of tDCS or sham coupled with language therapy. We correlated changes in the language network as well as in the default mode network (DMN) with language therapy outcome measures (letter accuracy in written naming). Significant tDCS effects in functional connectivity were observed between the stimulated area and other language network areas and between the language network and the DMN. TDCS over the left IFG lowered the connectivity between the above pairs. Changes in functional connectivity correlated with improvement in language scores (letter accuracy as a proxy for written naming) evaluated before and after therapy. These results suggest that one mechanism for anodal tDCS over the left IFG in PPA is a decrease in functional connectivity (compared to sham) between the stimulated site and other posterior areas of the language network. These results are in line with similar decreases in connectivity observed after tDCS over the left IFG in aging and other neurodegenerative conditions.

Schematic representation of the structure-based analysis performed. The T1-high resolution and the respective parcellation map (A, only cortical parcels represented) is co-registered (B) to the rsfMRI (C), therefore bringing the structural labels to this latter space (D), from where the fisher z-correlations between ROIs are extracted (E).

Box plots and scatter plots for behavioral scores by treatment group and variants. Y-axes are for absolute letter accuracy in % and X-axes are for time points. Different variants—nonfluent, semantic and logopenic—are separated in three columns. Treatment groups are color-coded as red for tDCS and blue for Sham. In the scatter plots, individuals are further coded as circles for tDCS and triangles for Sham. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)

Inter-Language-DMN network tDCS effects over sham in functional connectivity. Edge thickness is proportional to the absolute value of the tDCS effect, and the color map shows the value of the tDCS effect.

Scatter plot by treatment groups and PPA variants for change (after minus before) of absolute letter accuracy in % against change in connectivity for the IFG_triangularis_L: ITG_L pair. Variants are color-coded as red for nonfluent, green for semantic and blue for logopenic. Treatment assignments are coded as circles for tDCS and triangles for Sham. Fitted lines and pointwise confidence bands are plotted for each variant with the corresponding coded color and for all patients with the dot-dashed line and the color black. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)

Scatter plot by treatment groups and PPA variants for change (after minus before) of absolute whole-word accuracy in % against change in connectivity between the IFG_triangularis_L: ITG_L pair. Variants are color-coded as red for nonfluent, green for semantic and blue for logopenic. Treatment assignments are coded as circles for tDCS and triangles for Sham. Fitted lines and pointwise confidence bands are plotted for each variant with the corresponding coded color and for all participants with the dot-dashed line and the color black. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)